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Evaluating the Role of Ketamine/Esketamine in the Management of Major Depressive Disorder with Suicide Risk

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Abstract

Nearly 5% of individuals in the USA had serious thoughts of suicide in 2019 and over 30% of individuals suffering with major depressive disorder reported suicidal ideation with 2 million of those reporting suicidal ideation with some level of intent. However, options to treat depressed individuals considered at imminent risk of suicide remain limited. Until the recent approval of esketamine in the treatment of patients with major depressive disorder with serious suicidal thoughts or actions, no medications had been specifically evaluated for use in this population in the acute setting. This review discusses the history and the current understanding of the role of ketamine and esketamine in depression and suicidal ideation and behavior. It covers some of the pivotal studies in this field and provides a summary of their major findings. The trials of esketamine in patients with major depressive disorder with active suicidal ideation or behavior are the first large-scale trials in patients considered at imminent risk of suicide. As such, the design of these studies is by definition novel, a fact that complicates the interpretation of the data and assessment of the true clinical meaningfulness of the findings. Despite this, the findings in toto draw a consistent picture of benefits that appears to outweigh the potential risks of the treatment. The studies also serve to highlight the complexities and limitations associated with clinical trials aiming to test the ability of novel therapeutics to reduce the burden and risks in patients with suicide ideation and behavior.

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  1. Department of Psychiatry, Yale University School of Medicine, Yale Depression Research Program, Yale New Haven Hospital Interventional Psychiatry Service, Yale University, 100 York St., Suite 2J, New Haven, CT, 06511, USA

    Sina Nikayin & Gerard Sanacora

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  1. Sina Nikayin
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  2. Gerard Sanacora
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Correspondence to Gerard Sanacora.

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Funding

Funding supporting this work was provided by George D. Gross and Esther S. Gross Endowment and Yale New Haven Health.

Conflict of Interest

Dr. Nikayin has no disclosures to report. Dr. Sanacora has received consulting fees from Alkermes, Allergan, AstraZeneca, Avanier Pharmaceuticals, Axsome Therapeutics, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Clexio Biosciences, Denovo Biopharma, EMA Wellness, Engrail, Gilgamesh, Hoffmann-La Roche, Intra-Cellular Therapies, Janssen, Lundbeck, Merck, Minerva Neurosciences, Navitor Pharmaceuticals, Neurocrine, Novartis, Noven Pharmaceuticals, Otsuka, Perception Neuroscience, Praxis Therapeutics, Sage Pharmaceuticals, Seelos Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valeant, Vistagen Therapeutics, and XW Labs. He has also received research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson and Johnson, Hoffmann-La Roche, Merck, Naurex, Servier Pharmaceuticals, and Usona. No-cost medication was provided to Dr. Sanacora for a National Institutes of Health-sponsored study by Sanofi-Aventis. In addition, he holds shares in Biohaven Pharmaceuticals Holding Company and is a co-inventor on the patent “Glutamate agents in the treatment of mental disorders” (patent 8778979), and a filed patent for using mTOR inhibitors to augment the effects of antidepressants (filed on 20 August, 2018). Yale University, Dr. Sanacora’s and Dr. Nikayin’s institution, has a financial relationship with Janssen Pharmaceuticals and may receive financial benefits from this relationship.

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Dr Nikayin and Dr Sanacora contributed to the concept and design of the review and to the writing of the manuscript, approved the final version of the manuscript for submission/publication, and agree to be accountable for the work.

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Nikayin, S., Sanacora, G. Evaluating the Role of Ketamine/Esketamine in the Management of Major Depressive Disorder with Suicide Risk. CNS Drugs 35, 1069–1079 (2021). https://doi.org/10.1007/s40263-021-00851-8

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